Evidence map›Paper›PMID 32920226›Full record

ArticleRedox biology2020

Vitamin E treatment in NAFLD patients demonstrates that oxidative stress drives steatosis through upregulation of de-novo lipogenesis.

Maren C Podszun, Ahmad S Alawad, Shilpa Lingala, Nevitt Morris, Wen-Chun A Huang, Shanna Yang, Megan Schoenfeld, Adam Rolt, Ronald Ouwerkerk, Kristin Valdez and 15 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01792115 (Treatment for Non-Alcoholic Fatty Liver With Different Doses of Vitamin E), which is not on this map. Cited by 56 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 3 pooled it
8.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01792115 phase2completednot on this map

Treatment for Non-Alcoholic Fatty Liver With Different Doses of Vitamin E

TypeinterventionalSponsorNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Ran2013 to 2019Enrolled22ConditionsFatty LiverArmsVitamin E 200 IU/d, Vitamin E 400 IU/d, Vitamin E 800 IU/d, Diet and Exercise
3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 3 syntheses or guidelines pooled it, 105 citations in OpenAlex.

  1. Pooled it
  2. Vitamin E for people with non-alcoholic fatty liver disease.The Cochrane database of systematic reviews · 2024
    Pooled it
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  15. Endonuclease G promotes hepatic mitochondrial respiration by selectively increasing mitochondrial tRNAProceedings of the National Academy of Sciences of the United States of America · 2025
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  18. GNature communications · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors at 2 institutions in 1 country.

Maren C PodszunLiver and Energy Metabolism Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Ahmad S AlawadLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Shilpa LingalaLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Nevitt MorrisLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Wen-Chun A HuangLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Shanna YangNutrition Department, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Megan SchoenfeldNutrition Department, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Adam RoltLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Ronald OuwerkerkBiomedical and Metabolic Imaging Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Kristin ValdezLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Regina UmarovaLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Yanling MaLiver and Energy Metabolism Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Syeda Zaheen FatimaLiver and Energy Metabolism Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Dennis D LinLiver and Energy Metabolism Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Lakshmi S MahajanLiver and Energy Metabolism Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Niharika SamalaLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Pierre-Christian VioletMolecular and Clinical Nutrition Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Mark LevineMolecular and Clinical Nutrition Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Robert ShamburekCardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Ahmed M GharibBiomedical and Metabolic Imaging Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
David E KleinerLaboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
H Martin GarraffoClinical Mass Spectrometry Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Hongyi CaiClinical Mass Spectrometry Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Peter J WalterClinical Mass Spectrometry Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Yaron RotmanLiver and Energy Metabolism Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: rotmany@niddk.nih.gov.
National Institutes of Health · USNational Institutes of Health Clinical Center · US

Funding

Nonalcoholic Steatohepatitis: Natural History, Pathogenesis and TherapyZIADK075013 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI ROTMAN, YARON · 2009 to 2025
$19.1M
NLM NIH HHS HHSN276201200017C
6 · The paper itself

Abstract

Oxidative stress (OS) in non-alcoholic fatty liver disease (NAFLD) promotes liver injury and inflammation. Treatment with vitamin E (α-tocopherol, αT), a lipid-soluble antioxidant, improves liver injury but also decreases steatosis, thought to be upstream of OS, through an unknown mechanism. To elucidate the mechanism, we combined a mechanistic human trial interrogating pathways of intrahepatic triglyceride (IHTG) accumulation and in vitro experiments. 50% of NAFLD patients (n = 20) treated with αT (200-800 IU/d) for 24 weeks had a ≥ 25% relative decrease in IHTG by magnetic resonance spectroscopy. Paired liver biopsies at baseline and week 4 of treatment revealed a decrease in markers of hepatic de novo lipogenesis (DNL) that strongly predicted week 24 response. In vitro, using HepG2 cells and primary human hepatocytes, αT inhibited glucose-induced DNL by decreasing SREBP-1 processing and lipogenic gene expression. This mechanism is dependent on the antioxidant capacity of αT, as redox-silenced methoxy-αT is unable to inhibit DNL in vitro. OS by itself was sufficient to increase S2P expression in vitro, and S2P is upregulated in NAFLD livers. In summary, we utilized αT to demonstrate a vicious cycle in which NAFLD generates OS, which feeds back to augment DNL and increases steatosis. Clinicaltrials.gov: NCT01792115.

Indexed as

Non-alcoholic Fatty Liver DiseaseHumansLipogenesisLiverOxidative StressUp-RegulationVitamin EVitamin Ede novo lipogenesisNAFLDNon-alcoholic fatty liver diseaseOxidative stressS1PS2PVitamin E

Identifiers

PMID32920226
PMCPMC7494510
OpenAlexW3081550315

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.